Regulated Proteolysis of MutSγ Controls Meiotic Crossing Over.
Mol Cell
; 78(1): 168-183.e5, 2020 04 02.
Article
en En
| MEDLINE
| ID: mdl-32130890
ABSTRACT
Crossover recombination is essential for accurate chromosome segregation during meiosis. The MutSγ complex, Msh4-Msh5, facilitates crossing over by binding and stabilizing nascent recombination intermediates. We show that these activities are governed by regulated proteolysis. MutSγ is initially inactive for crossing over due to an N-terminal degron on Msh4 that renders it unstable by directly targeting proteasomal degradation. Activation of MutSγ requires the Dbf4-dependent kinase Cdc7 (DDK), which directly phosphorylates and thereby neutralizes the Msh4 degron. Genetic requirements for Msh4 phosphorylation indicate that DDK targets MutSγ only after it has bound to nascent joint molecules (JMs) in the context of synapsing chromosomes. Overexpression studies confirm that the steady-state level of Msh4, not phosphorylation per se, is the critical determinant for crossing over. At the DNA level, Msh4 phosphorylation enables the formation and crossover-biased resolution of double-Holliday Junction intermediates. Our study establishes regulated protein degradation as a fundamental mechanism underlying meiotic crossing over.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Intercambio Genético
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Proteínas de Saccharomyces cerevisiae
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Complejo de la Endopetidasa Proteasomal
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Proteínas de Unión al ADN
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Meiosis
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos